Topical formulations, including ointments, creams, lotions, pastes, oils and gels, are used in the dermal and transdermal (through the skin) delivery of active drugs such as, for example, hydrocortisone and nitroglycerin to sites of action in the body.
Topical application of a drug is advantageous because it allows localized delivery of the therapeutic agent directly to the desired site, thus, increasing bioavailability (the extent to which a drug reaches its site of action), reducing drug side effects and loss of therapeutic efficiency and increasing patient compliance.
An important parameter in the development of dermal and transdermal drug delivery formulations is the rate at which the active drug is delivered. This parameter is measured in vitro (literally “in glass”, meaning in the laboratory as opposed to in the living body) by drug release and/or dissolution testing. The United States Pharmacopeia specifies FDA approved standards for equipment and procedures used for dissolution testing.
It has been convention that a sample of the formulation, be it a cream, lotion, ointment, gel or other medium containing the drug or active agent, is placed on one side of a permeable membrane which simulates the barrier, presented by the skin, between the drug and the site of action. The membrane could be formed from actual skin taken from a laboratory animal, or a synthetic material such as polysulfone, acrylic polymer, glass fiber or PTFE to cite a few examples. The side of the membrane opposite the test sample is brought into contact with a liquid receptor media, and the drug or other active agent in the formulation diffuses through the membrane and dissolves into the receptor media. The concentration of the drug in the receptor media is measured periodically over time to establish the rate at which it is delivered into the media, thus, providing an indication of its delivery rate in actual use.
There are various devices currently available to hold the test sample during dissolution testing, and all of them suffer from one or more serious disadvantages. For example, some of the devices are complicated, having many interfitting parts which can be difficult and tedious to assemble. Assembly must be done by experienced technicians using great care to avoid puncturing, tearing or wrinkling the delicate membranes held in the devices. The devices are often loaded with the test sample before they are fully assembled, thus, preventing simple visual checks from being performed after assembly to ensure that the proper quantity of sample has been loaded and that the entire membrane surface is covered by the sample. In use, the devices are typically fully immersed in the vessel holding the receptor media with the membrane located facing upward at the top of the device. In this configuration, gravity works to pull the test sample out of contact with the membrane, air pockets can form adjacent to the membrane preventing contact between sample and membrane and causing variability of test measurements. This configuration also results in a “dead volume” of the receptor media forming under the device, the media in the “dead volume” being stagnant and not participating in the dissolution of the sample and, thus, being a source of inaccuracy in the measurements.
Clearly, there is a need for an improved test sample holder for dissolution testing which is simple in construction, is easy to assemble, minimizes the potential for damage to the membrane, allows for visual observation of the test sample, avoids the creation of dead volumes of receptor media or air pockets and is useable with standard United States Pharmacopeia dissolution equipment and procedures.